Many inflammatory diseases of the intestinal wall are caused or influenced by changes in the intestinal microbiota and/or an impaired interaction between the intestinal microbiota and the intestines. Such intestinal inflammations occur in humans, e.g., inflammatory bowel diseases (IBD), such as Crohn's disease or ulcerative colitis, but also in other mammals (e.g., chronic idiopathic colitis in dogs). These diseases are based on complex immunological processes which are not fully understood.
However, changes in, and impaired interactions of, the intestinal microbiota can also be causative factors in a number of other diseases. Examples include atopic diseases, such as atopic eczema, allergic conditions or asthma (see e.g., Bisgaard et al. 2011, J. Allergy Clin. Immunol. 128:646; Iebba et al. 2011, Dig. Dis. 29:531; Abrahamsson et al. 2012, J. Allergy Clin. Immunol. 129:434; Candela et al. 2012, BMC Microbiol. 12:95; Olszak et al. 2012, Science 336:489), as well as metabolic diseases with an inflammatory component, such as arteriosclerosis with resulting coronary heart diseases, adiposity or diabetes (Ott et al. 2006, Circulation 113:929; Koren et al. 2011, PNAS 108 Suppl 1:4592; for reviews see Caesar et al. 2010, J. Intern. Med. 268:320; and Vrise et al. 2010, Diabetologia 53:606).
Although data indicate a pathological or pathophysiological relationship between the intestinal microbiota and various diseases, it has not been understood how to influence the microbiota in a way that would beneficially impact associated diseases.
Nicotinamide (nicotinic acid amide) and the related nicotinic acid (niacin, vitamin B3) have been used for the therapy of niacin deficiency diseases (e.g., pellagra) for decades. It is known that pellagra may be accompanied by intestinal inflammation, which is ameliorated after niacin administration, where the therapeutic principle is restoring the vitamin cofactors needed for normal intestinal cell growth, differentiation and development (Segal et al. 1986, Int. J. Colorectal Dis. 1:238; and Clayton et al. 1991, Eur. J. Pediatr. 150:498).
Formulations containing 5-ASA have also been used for decades in the therapy of IBD, in particular in ulcerative colitis (recently reviewed by: Sonu et al. 2010, Gastroenterol. Clin. North Am. 39:559; Klotz 2012, Arzneimittelforschung/Drug Research 62:53). The mechanism of action of 5-ASA is still unclear, but is considered to be a multifactorial influence on the immune system and inflammatory processes in the inflamed mucosa.